This proposal can be considered as containing two components. The first component is concerned with the in vivo replication of the avian sarcoma virus genome. In the cytoplasm of the infected cell the plus RNA is first transcribed into minus DNA and thence a plus DNA synthesized. Experiments are proposed to examine the initiation and termination of these DNA species and also the possible role of the RNase H. Subsequently in the nucleus of the infected cell, covalently closed circular double-stranded DNA species are formed. These will be isolated, labeled in vitro, and subsequently analyzed to create a map of restriction enzyme sites. An examination will also be made of viral DNA integrated into duck cells in an attempt to clarify those sites on the cellular genome at which integration occurs. The second component of this proposal is directed towards an analysis of the spontaneous age-related leukemia of AKR mice. It has been found that in target tissues of leukemic mice the transcription into RNA of the integrated endogenous AKR genome is enhanced more than one thousand-fold with respect to non-target tissues. An analysis will be made of the viral DNA sequences in target tissues with attention being given particularly to possible reorganization of viral sequences as a correlate of enhanced transcription into RNA.